Despite the importance of synaptic transmission in nervous system function, the mechanism of neurotransmitter release and the mechanisms of variable synaptic efficacy are poorly understood. The goals of the proposed research are (1) to test for differential effects of temperature, metabolic inhibitors, (Ca) and osmolarity on the magnitude and time course of facilitation, post-tetanic potentiation (PTP), and augmentation of transmitter release during and following repetitive stimulation, (2) to determine the relationship between these three types of transmitter release, (3) to determine if a feedback system operates to regulate transmitter release. Depending on the experiment, estimates of the amount of transmitter released at the vertebrate neuromuscular junction will be made from measurements of end-plate potentials recorded intracellularly or extracellularly or from measurements of end-plate currents recorded under voltage clamp. Models for the mechanism of transmitter release in terms of the calcium hypothesis and quantal hypothesis will be formulated and evaluated by comparing experimental results to predicted results obtained by simulation of the models on a digital computer. BIBLIOGRAPHIC REFERENCES: Magleby, K.L. & Zengel, J.E. (1975). A dual effect of repetitive stimulation on post-tetanic potentiation of transmitter release at the frog neuromuscular junction. J. Physiol. 245, 163-182. Magleby, K.L. & Zengel, J.E. (1975). A quantitative description of tetanic and post-tetanic potentiation of transmitter release at the frog neuromuscular junction. J. Physiol. 245, 183-208.